The phenotype analysis of infertile men with complete AZFc deletion

Purpose: Azoospermia factors (AZF) are located on the long arm of Y chromosome and have been divided into three regions, namely AZFa, AZFb and AZFc. While the AZFc region is the most commonly deleted because its structure is composed of many palindromes. Deletion of the AZFc region is found in about 13% of azoospermic and in 6% of severely oligozoospermic men. Complete AZFc deletions were accounted for by intrachromosomal recombination between the b2 and b4 amplicons. Deletions of the entire AZFc region result in loss of all four DAZ copies which are the first spermatogenesis genes identified on the human Y chromosome. Males with Y chromosome infertility usually have no obvious symptoms, although physical examination may demonstrate smaller testes. Currently, literature on Y deletions have no conception about the phenotypic effects of the deletions. We presented the phenotypes and treatment outcome of infertile men with complete AZFc deletion in our hospital.

Materials and Methods: We retrospectively reviewed patients with complete AZFc deletion (b2/b4) deletion presenting with either non-obstructive azoospermia (NOA) or oligoasthenoteratozoospermia (OAT) from 2008 to 2014. The phenotypic elements such as age, karyotyping, hormone profile, sperm analysis parameters, findings at physical examination (status of testis, vas, varicocele), endocrine profile and sperm retrieval rate were analyzed. Testis volume was divided into 2 categories by a cutoff value at 12ml.

Results: Totally 41 patients, mean age 35.1 y/o, were collected. There were 29 NOA and 12 OAT patients. In the 29 NOA patients, 2 had sperm recovered from semen after a period of medical treatment. Eighteen patients received microdissection testicular sperm extraction (mTESE) and 13 had successful sperm retrieval. The sperm retrieval rate for NOA patients was 15/20 (75%). For all patients with AZFc deletion, the sperm retrieval rate was 84.4%. Mean testicular volume was 14.4 ± 4.5 ml for left side and 14.6 ± 4.6 for right side. The mean semen volume was 3.9 ± 1.3 ml. The mean FSH was 15.3 ± 9.6 mIU/ml, LH was 6.7 ± 3.3 mIU/ml, testosterone was 4.3 ± 1.8 ng/ml, prolactin was 11.6 ± 5.9 ng/ml, and E2 was 24.8 ± 10.4 pg/ml. The only statistically significant factor for predicting sperm in semen was testis volume larger than 12ml (P = 0.047). There was no identifiable predicting factor for success sperm retrieval in NOA patients.

Conclusion: From our data, although with limited patients number, the sperm retrieval rate was 84.4% in all patients and 75% in NOA via mTESE procedure. Testis volume larger than 12ml is a predicting factor for sperm appearance in semen for patients with complete AZFc deletion.